Extracorporeal, low-energy focused ultrasound for noninvasive and nondestructive targeted hyperthermia

The benefits of hyperthermia are well known as both a primary treatment modality and adjuvant therapy for treating cancer. Among the different techniques available, high-intensity focused ultrasound is the only noninvasive modality that can provide local hyperthermia precisely at a targeted location at any depth inside the body using image guidance. Traditionally, focused ultrasound exposures have been provided at high rates of energy deposition for thermal ablation of benign and malignant tumors. At present, exposures are being evaluated in pulsed mode, which lower the rates of energy deposition and generate primarily mechanical effects for enhancing tissue permeability to improve local drug delivery. These pulsed exposures can be modified for low-level hyperthermia as an adjuvant therapy for drug and gene delivery applications, as well as for more traditional applications such as radiosensitization. In this review, we discuss the manner by which focused ultrasound exposures at low rates of energy deposition are being developed for a variety of clinically translatable applications for the treatment of cancer. Specific preclinical studies will be highlighted. Additional information will also be provided for optimizing these exposures, including computer modeling and simulations. Various techniques for monitoring temperature elevations generated by focused ultrasound will also be reviewed.